PMID- 29856817
OWN - NLM
STAT- MEDLINE
DCOM- 20190111
LR  - 20190111
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 6
DP  - 2018
TI  - Low-molecular-weight heparin venous thromboprophylaxis in critically ill patients 
      with renal dysfunction: A subgroup analysis of the PROTECT trial.
PG  - e0198285
LID - 10.1371/journal.pone.0198285 [doi]
LID - e0198285
AB  - INTRODUCTION: There is concern about excessive bleeding when low-molecular-weight 
      heparins (LMWHs) are used for venous thromboembolism (VTE) prophylaxis in renal 
      dysfunction. Our objective was to evaluate whether LMWH VTE prophylaxis was safe 
      and effective in critically ill patients with renal dysfunction by conducting a 
      subgroup analysis of PROTECT, a randomized blinded trial. METHODS: We studied 
      intensive care unit (ICU) patients with pre-ICU dialysis-dependent end-stage 
      renal disease (ESRD; pre-specified subgroup; n = 118), or severe renal 
      dysfunction at ICU admission (defined as ESRD or non-dialysis dependent with 
      creatinine clearance [CrCl] <30 ml/min; post hoc subgroup; n = 590). We compared 
      dalteparin, 5000 IU daily, with unfractionated heparin (UFH), 5000 IU twice 
      daily, and considered outcomes of proximal leg deep vein thrombosis (DVT); 
      pulmonary embolism (PE); any VTE; and major bleeding. Adjusted hazard ratios [HR] 
      were calculated using Cox regression. RESULTS: In patients with ESRD, there was 
      no significant difference in DVT (8.3% vs. 5.2%, p = 0.76), any VTE (10.0% vs. 
      6.9%; p = 0.39) or major bleeding (5.0% vs. 8.6%; p = 0.32) between UFH and 
      dalteparin. In patients with severe renal dysfunction, there was no significant 
      difference in any VTE (10.0% vs. 6.4%; p = 0.07) or major bleeding (8.9% vs. 
      11.0%; p = 0.66) but an increase in DVT with dalteparin (7.6% vs. 3.7%; p = 
      0.04). Interaction p-values for comparisons of HRs (ESRD versus not) were 
      non-significant. CONCLUSIONS: In critically ill patients with ESRD, or severe 
      renal dysfunction, there was no significant difference in any VTE or major 
      bleeding between UFH and dalteparin. Patients with severe renal dysfunction who 
      received dalteparin had more proximal DVTs than those on UFH; this finding did 
      not hold in patients with ESRD alone.
FAU - Pai, Menaka
AU  - Pai M
AUID- ORCID: 0000-0002-6053-689X
AD  - Department of Medicine, McMaster University, Hamilton, Canada.
AD  - Hamilton Regional Laboratory Medicine Program, Hamilton, Canada.
AD  - Department of Pathology and Molecular Medicine, McMaster University, Hamilton, 
      Canada.
FAU - Adhikari, Neill K J
AU  - Adhikari NKJ
AD  - Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, 
      Canada.
AD  - Interdepartmental Division of Critical Care Medicine, University of Toronto, 
      Toronto, Canada.
FAU - Ostermann, Marlies
AU  - Ostermann M
AD  - Department of Critical Care, Guys and St Thomas Hospital, London, England.
FAU - Heels-Ansdell, Diane
AU  - Heels-Ansdell D
AD  - Department of Health Research Methods, Evidence, and Impact, McMaster University, 
      Hamilton, Canada.
FAU - Douketis, James D
AU  - Douketis JD
AD  - Department of Medicine, McMaster University, Hamilton, Canada.
AD  - Department of Health Research Methods, Evidence, and Impact, McMaster University, 
      Hamilton, Canada.
FAU - Skrobik, Yoanna
AU  - Skrobik Y
AD  - Department of Medicine, Hopital Maisonneuve Rosemont, Montreal, Canada.
FAU - Qushmaq, Ismael
AU  - Qushmaq I
AD  - Department of Medicine, King Faisal Specialist Hospital & Research Center, 
      Jeddah, Saudi Arabia.
FAU - Meade, Maureen
AU  - Meade M
AD  - Department of Medicine, McMaster University, Hamilton, Canada.
AD  - Department of Health Research Methods, Evidence, and Impact, McMaster University, 
      Hamilton, Canada.
FAU - Guyatt, Gordon
AU  - Guyatt G
AD  - Department of Medicine, McMaster University, Hamilton, Canada.
AD  - Department of Health Research Methods, Evidence, and Impact, McMaster University, 
      Hamilton, Canada.
FAU - Geerts, William
AU  - Geerts W
AD  - Department of Medicine, University of Toronto, Toronto, Canada.
FAU - Walsh, Michael W
AU  - Walsh MW
AD  - Department of Medicine, McMaster University, Hamilton, Canada.
AD  - Department of Health Research Methods, Evidence, and Impact, McMaster University, 
      Hamilton, Canada.
FAU - Crowther, Mark A
AU  - Crowther MA
AD  - Department of Medicine, McMaster University, Hamilton, Canada.
AD  - Hamilton Regional Laboratory Medicine Program, Hamilton, Canada.
AD  - Department of Pathology and Molecular Medicine, McMaster University, Hamilton, 
      Canada.
FAU - Friedrich, Jan O
AU  - Friedrich JO
AD  - Interdepartmental Division of Critical Care Medicine, University of Toronto, 
      Toronto, Canada.
AD  - Department of Medicine, University of Toronto, Toronto, Canada.
FAU - Burry, Lisa
AU  - Burry L
AD  - Mount Sinai Hospital, Toronto, Canada.
FAU - Bellomo, Rinaldo
AU  - Bellomo R
AD  - Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), Monash 
      University, Melbourne, Australia.
FAU - Brandao da Silva, Nilton
AU  - Brandao da Silva N
AD  - Moinhos de Vento Hospital, Porto Alegre, Brazil.
FAU - Costa Filho, Rubens
AU  - Costa Filho R
AD  - Pro Cardiaco Hospital, PROCEP, Rio de Janeiro, Brazil.
FAU - Cox, Michael J
AU  - Cox MJ
AD  - St. John's Mercy Medical Center, St. Louis, Missouri, United States of America.
FAU - Alves Silva, Suzana
AU  - Alves Silva S
AD  - Pro Cardiaco Hospital, PROCEP, Rio de Janeiro, Brazil.
FAU - Cook, Deborah J
AU  - Cook DJ
AD  - Department of Medicine, McMaster University, Hamilton, Canada.
AD  - Department of Health Research Methods, Evidence, and Impact, McMaster University, 
      Hamilton, Canada.
CN  - PROTECT (Prophylaxis for Thromboembolism in Critical Care Trial) Investigators
LA  - eng
GR  - #MCT78568/Canadian Institute Health Research/International
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180601
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Anticoagulants)
RN  - 0 (Heparin, Low-Molecular-Weight)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anticoagulants/*therapeutic use
MH  - Chemoprevention/*methods
MH  - Critical Care/methods
MH  - Critical Illness/*therapy
MH  - Female
MH  - Heparin, Low-Molecular-Weight/*therapeutic use
MH  - Humans
MH  - Kidney Failure, Chronic/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Venous Thromboembolism/*prevention & control
PMC - PMC5983525
COIS- This study received support from Pfizer Canada, which provided dalteparin for 
      Canadian centers, and Eisai, Inc, which provided dalteparin for centers in the 
      United States. Neither group played a role in the design, conduct, analysis, 
      interpretation or write-up of this trial. The authors have no other relevant 
      declarations relating to employment, consultancy, patents, products in 
      development, or marketed products. The competing interests declared here do not 
      alter our adherence to PLOS ONE policies on sharing data and materials.
EDAT- 2018/06/02 06:00
MHDA- 2019/01/12 06:00
PMCR- 2018/06/01
CRDT- 2018/06/02 06:00
PHST- 2017/12/19 00:00 [received]
PHST- 2018/05/13 00:00 [accepted]
PHST- 2018/06/02 06:00 [entrez]
PHST- 2018/06/02 06:00 [pubmed]
PHST- 2019/01/12 06:00 [medline]
PHST- 2018/06/01 00:00 [pmc-release]
AID - PONE-D-17-38647 [pii]
AID - 10.1371/journal.pone.0198285 [doi]
PST - epublish
SO  - PLoS One. 2018 Jun 1;13(6):e0198285. doi: 10.1371/journal.pone.0198285. 
      eCollection 2018.